Abstract
How a cell maintains transcriptional fidelity across the cell cycle has remained an enduring mystery in biology. One of the challenges arises during mitosis when chromatin becomes highly condensed and transcription is shut off. How do the new daughter cells re-establish the original transcription program? Here, we report that the TATA-binding protein (TBP), a key component of the core transcriptional machinery, remains bound globally to promoters of active genes in ES cells during mitosis. Using single molecule imaging in live cells, we observed that mitotic binding of TBP is highly stable, with an average residence time of several minutes. This stable binding is in stark contrast to typical TFs with residence times of seconds. To test the functional effect of mitotic TBP binding, we used a drug-inducible degron system and found that TBP binding promotes the association of RNA Polymerase II with mitotic chromosomes, and facilitates transcriptional reactivation following mitosis. Taken together, these results suggest that the core transcriptional machinery maintains global transcriptional memory during mitosis.
